The Lens and Cataract Biology Section studies the biology of the normal lens, the mechanisms involved in cataractogenesis, and works to develop and test potential therapeutic agents for the prevention or retardation of cataract development. During the past year, Drs. Qiufang Cheng, Paul Russell and myself have tested in organ culture several prodrug preparations of the potential anti-cataract drug Tempol-H, which we identified previously. The prodrugs are intended to facilitate penetration of the cornea so that topical application to the eye will be feasible. Initial studies in live animals appear promising, but data is still being collected. We hope to soon identify a prodrug formulation for testing of toxicity and efficacy in animals. We continue to study the effects of statins, cholesterol-lowering drugs, on the lens. Our data indicate that inhibition of protein prenylation by those compounds can be deleterious to the lens. Dr. Cheng has recently demonstrated a stimulation of apoptosis in the epithelial cells of lenses exposed to lovastatin. The apoptosis and other cataractogenic effects on the lens are strongly inhibited by the addition of geranylgeranyl pyrophosphate. This indicates that decreased prenylation, probably of small GTPases of the Ras superfamily, is a primary factor in these effects on the lens. With interest in the statins as therapeutic agents for other conditions including Alzheimer?s Disease and macular degeneration expanding, our studies have increased potential significance.